ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.1351G>A (p.Ala451Thr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001110792.2(MECP2):c.1351G>A (p.Ala451Thr)
Variation ID: 143458 Accession: VCV000143458.47
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154030513 (GRCh38) [ NCBI UCSC ] X: 153295964 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 23, 2014 May 1, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.1351G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Ala451Thr missense NM_004992.4:c.1315G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Ala439Thr missense NM_001316337.2:c.1036G>A NP_001303266.1:p.Ala346Thr missense NM_001369391.2:c.1036G>A NP_001356320.1:p.Ala346Thr missense NM_001369392.2:c.1036G>A NP_001356321.1:p.Ala346Thr missense NM_001369393.2:c.1036G>A NP_001356322.1:p.Ala346Thr missense NM_001369394.2:c.1036G>A NP_001356323.1:p.Ala346Thr missense NM_001386137.1:c.646G>A NP_001373066.1:p.Ala216Thr missense NM_001386138.1:c.646G>A NP_001373067.1:p.Ala216Thr missense NM_001386139.1:c.646G>A NP_001373068.1:p.Ala216Thr missense NC_000023.11:g.154030513C>T NC_000023.10:g.153295964C>T NG_007107.3:g.111591G>A LRG_764:g.111591G>A LRG_764t1:c.1351G>A LRG_764p1:p.Ala451Thr LRG_764t2:c.1315G>A LRG_764p2:p.Ala439Thr P51608:p.Ala439Thr AJ132917.1:c.1315G>A - Protein change
- A439T, A451T, A346T, A216T
- Other names
- NM_001110792.2(MECP2):c.1351G>A
- p.Ala451Thr
- Canonical SPDI
- NC_000023.11:154030512:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00024
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00028
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MECP2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1825 | 2148 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely benign (1) |
no assertion criteria provided
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Apr 26, 2016 | RCV000132986.11 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 23, 2019 | RCV000146352.26 | |
Likely benign (1) |
no assertion criteria provided
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Apr 26, 2016 | RCV000170236.10 | |
Likely benign (1) |
no assertion criteria provided
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Apr 26, 2016 | RCV000170237.10 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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May 1, 2023 | RCV000471943.29 | |
Benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV001089023.14 | |
Benign (1) |
criteria provided, single submitter
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May 31, 2018 | RCV002312624.9 | |
Benign (1) |
criteria provided, single submitter
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Aug 14, 2023 | RCV003380467.1 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 30, 2021 | RCV003952688.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000193628.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Likely benign
(May 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000708129.2
First in ClinVar: Mar 08, 2017 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(Jan 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157690.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
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Benign
(Mar 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000513574.6
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 12566531, 10767337, 12872250, 12384770, 16763963)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Severe neonatal-onset encephalopathy with microcephaly
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000556733.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024 |
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Likely benign
(Jun 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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MECP2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004770033.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(May 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001150510.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
MECP2: BP4, BS2
Number of individuals with the variant: 3
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Benign
(May 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000846373.5
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(Aug 14, 2023)
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criteria provided, single submitter
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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Centre for Population Genomics, CPG
Accession: SCV004098740.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria.Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel … (more)
This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria.Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0, this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 2.0 (BA1). (less)
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Likely benign
(Apr 26, 2016)
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no assertion criteria provided
Method: research
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X-linked intellectual disability-psychosis-macroorchidism syndrome
Affected status: unknown
Allele origin:
maternal
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RettBASE
Accession: SCV000187970.3
First in ClinVar: Aug 17, 2014 Last updated: Jan 30, 2017 |
Number of individuals with the variant: 7
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Likely benign
(Apr 26, 2016)
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no assertion criteria provided
Method: research
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Autism, susceptibility to, X-linked 3
Affected status: unknown
Allele origin:
maternal
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RettBASE
Accession: SCV000222567.2
First in ClinVar: Apr 22, 2015 Last updated: Jan 30, 2017 |
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Likely benign
(Apr 26, 2016)
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no assertion criteria provided
Method: research
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Hereditary attention deficit-hyperactivity disorder
Affected status: unknown
Allele origin:
maternal
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RettBASE
Accession: SCV000222566.2
First in ClinVar: Apr 22, 2015 Last updated: Jan 30, 2017 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927574.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001970455.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A new cohort of MECP2 mutation screening in unexplained mental retardation: careful re-evaluation is the best indicator for molecular diagnosis. | Donzel-Javouhey A | American journal of medical genetics. Part A | 2006 | PMID: 16763963 |
Mutations and polymorphisms in the human methyl CpG-binding protein MECP2. | Miltenberger-Miltenyi G | Human mutation | 2003 | PMID: 12872250 |
Developmental delay and the methyl binding genes. | Turner H | Journal of medical genetics | 2003 | PMID: 12566531 |
Mutation analysis of the coding sequence of the MECP2 gene in infantile autism. | Beyer KS | Human genetics | 2002 | PMID: 12384770 |
Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. | Cheadle JP | Human molecular genetics | 2000 | PMID: 10767337 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MECP2 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d98bae0e-ec76-41ea-8546-6a5160db5c9c | - | - | - | - |
Text-mined citations for rs61753973 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.